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W W Mullins

Publications and source records attributed to W W Mullins.

5 recordsLinked to original sources

Soluble immune complexes in lupus mice: clearance from blood and estimation of formation rates.

Elevated levels of circulating immune complexes (IC) occur in patients with systemic lupus erythematosus (SLE) and in several strains of mice that spontaneously develop a lupus-like illness. An increase in circulating IC might occur as a result of increased IC formation or decreased IC clearance. Previous work with one murine lupus strain, NZB/W, demonstrated normal clearance of soluble IC. We studied the in vivo behavior of stable model IgG IC in two murine lupus strains. MRL/l and BXSB, and in two normal strains, C3H/HeN and BALB/c. IC were injected intravenously, and blood radioactivity was measured over 3 hr. A clearance curve was derived for each mouse using the Marquardt-Levenberg curve-fitting method. A formula is derived which predicts the formation rate of IC in each animal from the blood level of IC and the clearance curve parameters. All mice exhibited biphasic exponential clearance of IC over 3 hr. Clearance of IC was significantly slower in MRL/l mice than in normal strains (P less than 0.02), and clearance in BXSB mice was significantly faster than in normals (P less than 0.02). However, the derived formula suggests that the observed differences in IC clearance have only a small effect on the blood levels of IC in the mice studied, and therefore suggests that the major factor which accounts for increased blood levels of IC in lupus mice is an increase in the IC formation rate.

Albumins↗

Failure of methotrexate and methylprednisolone to alter the clearance of model immune complexes.

We evaluated the effect of methotrexate (MTX) and methylprednisolone (MP) on reticuloendothelial system (RES) clearance of soluble model immune complexes (IC) in BALB/C mice. MTX was administered by intraperitoneal route either as a single dose (0.5 mg/kg) or as 10 alternate day doses (0.1 or 0.5 mg/kg), MP as a single intravenous (IV) bolus (50 mg/kg) with normal saline used as a control. Mice were then injected IV with radiolabelled IgG anti-DNP covalently crosslinked IC. Blood radioactivity was measured over a 3 h period at which time organ uptake, corrected for blood contamination, was determined. Clearance curves for each mouse were derived using the Marquardt-Levenberg curve fitting method. No significant differences in IC clearance or organ uptake were found between drug and control groups at any drug dose or time period. Our findings argue against an influence of MP and MTX on immunospecific clearance of soluble IC.

Animals↗

Monocyte receptors for the Fc portion of IgG are increased in systemic lupus erythematosus.

Defective clearance of IgG-sensitized particles has been documented in systemic lupus erythematosus (SLE). This defect may be of pathogenetic significance because it allows the prolonged circulation of endogenous immune complexes with subsequent tissue deposition. To assess the possible contribution of a genetically determined defect in phagocyte Fc-IgG receptor expression or immune complex saturation of Fc-IgG receptors to impaired clearance, we used a well-characterized monomer binding assay to quantitate monocyte Fc-IgG receptors in normal controls and in 26 patients with SLE. Mean monocyte Fc-IgG receptor numbers were increased in both male and female SLE patients relative to normal controls. Increasing receptor numbers correlated positively with increasing clinical disease activity and increasing titers of antibody to native, double-stranded DNA. No significant correlation was found between any single disease symptom, organ system involvement, drug therapy, antigenic C3 levels, or immune complex levels and receptor number. A negative correlation was noted between Fc-IgG receptor binding affinity constants in SLE patients and clinical disease activity, but none of the observed affinity constants fell outside the 95% confidence normal range, and the mean affinity constants for patients both with and without active disease were not significantly different from controls. Our results are inconsistent with a genetically determined defect in Fc-IgG receptor elaboration by mononuclear phagocytes, and suggest that simple immune complex saturation does not underlie abnormal Fc-IgG-mediated clearance in SLE.

Adult↗

Spatial summation effects on two-component grating thresholds.

Some experimental studies of subthreshold summation between sinusoidal grating components have been interpreted as showing very narrow channel bandwidths in human visions. This paper discusses an alternative interpretation of these experiments based on consideration of probability-summation effects among spatially distributed detectors. We conclude that frequency-selective channels must still be hypothesized in order to fit the data, but the channel bandwidth may be much wider than earlier interpretations suggest.

Humans↗

Convexity theorem for subthreshold stimuli in linear models of visual contrast detection.

Under the general assumption that visual contrast detection occurs by a parallel array of linear detectors, either without probability summation or with probability summation of a commonly assumed type, it is shown that the set of functions representing subthreshold stimuli must be convex. Thus, for example, a planar plot of the threshold locus using multiples of any two functions as axes, must be convex (cannot bulge inward). If experimental evidence to the contrary were discovered, it would rule out detection by parallel linear detectors of the above type. One possible kind of such evidence would be an inward cusp of the threshold locus corresponding to one of a special class of stimuli to which the visual system might be specifically sensitive.

Humans↗